Could Autism be prevented in pregnancy?

Mark Waghorn

Autism could be prevented during pregnancy - by changing women's gut bacteria, according to new research.

Mothers-to-be who suffer an infection are up to three times more likely to have a child with the disorder - and now scientists may have found out why.

It triggers inflammation in those with particular types of bugs in their microbiome - harming development of the unborn baby's brain.

In experiments the same team even identified these specific changes that produce autistic-like behaviours in mice.

The breakthrough sheds fresh light on the link between infections in pregnancy and autism which has been a mystery for years.

Only offspring of mice with one specific harmless bacteria displayed autistic symptoms and had the alterations to their brain.

When the researchers killed the bugs - known as segmented filamentous bacteria - with antibiotics the mice produced normal offspring.

If further validated in human studies the findings could lead to reducing the risk of autism.

This would involve blocking the function of certain strains of bacteria found in the maternal gut, said the researchers.

They cause inflammation by producing immune cells known as Th17.

Senior author Professor Jun Huh said: "This data strongly suggests that perhaps certain mothers who happen to carry these types of Th17 cell-inducing bacteria in their gut may be susceptible to this inflammation-induced condition."

The discoveries published in two papers in Nature add to growing evidence infections during pregnancy can cause autism because of the mother's immune response - the inflammation.

They also offer hope of new treatments - or possibly even a cure.

Co-senior author Prof Gloria Choi, Massachusetts Institute of Technology's McGovern Institute for Brain Research, said: "We identified a very discrete brain region that seems to be modulating all the behaviours associated with this particular model of neurodevelopmental disorder."

In 2010 a large scale study of all children born in Denmark between 1980 and 2005 found those whose mothers had a severe viral infection during the first three of pregnancy had a threefold risk for autism.

Serious bacterial infections during the second 'trimester' were linked with a 42 percent increase in risk. They include flu, viral gastroenteritis and severe urinary tract infections.

Last year Prof Choi and Prof Huh found Th17 cells produce a chemical called IL-17 in pregnant mice which affects brain cells in the developing foetus.

This leads to irregularities they call "patches" in parts of the cortex which controls thoughts and actions.

Their latest research suggested these were responsible for the autistic-style problems seen in the mice such as repetitive behaviour and impaired sociability.

The patches are most common in a part of the brain known as S1DZ. Part of the somatosensory cortex, this region is believed to be responsible for sensing where the body is in space.

In these patches populations of cells called interneurons - which express a protein called parvalbumin - are reduced.

Interneurons are responsible for controlling the balance of excitation and inhibition in the brain. The changes found in the cortical patches caused over-excitement in S1DZ.

When the researchers restored normal levels of brain activity in this area they were able to reverse the behavioral abnormalities.

They were also able to induce the behaviors in otherwise normal mice by over-stimulating neurons in S1DZ.

The researchers also discovered S1DZ sends messages to two other brain regions - the temporal association area of the cortex and the striatum.

When the researchers blocked neurons connected to the former and latter respectively it reversed anti-social and repetitive behaviours.

The second paper delved into why not all mothers who experience severe infection end up having a child with autism.

Similarly not all the mice in the maternal inflammation model developed behavioural abnormalities.

Prof Choi said: "This suggests inflammation during pregnancy is just one of the factors. It needs to work with additional factors to lead all the way to that outcome."

A key clue was when immune systems in some of the pregnant mice were stimulated, they began producing IL-17 within a day.

Prof Huh, formerly of Massachusetts Medical School and now at Harvard Medical School, said: "Normally it takes three to five days because IL-17 is produced by specialised immune cells and they require time to differentiate."

"We thought that perhaps this cytokine is being produced not from differentiating immune cells, but rather from pre-existing immune cells."

Previous studies in mice and humans have found populations of Th17 cells in the intestines of healthy individuals.

These cells, which help to protect the host from harmful microbes, are thought to be produced after exposure to particular types of harmless bacteria that associate with the epithelium.

Humans can also carry strains of gut bacteria known to drive production of Th17 cells, and the researchers plan to investigate whether the presence of these bacteria is associated with autism.

Autism Spectrum Disorder (ASD) can cause a wide range of symptoms including problems with social interaction and communication.

It's estimated about 1 in every 100 people in the UK has ASD. More boys are diagnosed with it than girls.

There's no 'cure for ASD, but a range of educational and behavioural support programmes can help people with the condition.

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